PROJECT SUMMARY Down syndrome (DS) is a common genetic disorder occurring in approximately 1 in 700 births. Children with DS are smaller at birth and grow at a slower rate in length/height, weight and head circumference, than other children. Growth assessment is an important primary care screening tool to assess a child's general state of health, the impact of current medical conditions and to detect early signs of as yet undiagnosed medical conditions (e.g., hypothyroidism, hydrocephalus) in a timely manner. Weight-for-length in infants and body mass index (BMI) in older children and adolescents are also important screening tools for nutritional status assessment across the lifespan because of the risk of failure to thrive in infancy and obesity at older ages. Current growth charts for U.S. children with DS are available but outdated. Advances in health care and improved life expectancy of children with DS have occurred in the past few decades, and there is a well- recognized need for revised charts for growth in length, height, weight, head circumference, weight-for-length and body mass index. In addition, the recognized racial difference in life expectancy in people with DS underscores the importance of developing growth charts that have a more accurate representation of race and ethnic groups than previously published charts. Moreover, new charts should be based on research quality measurements, with an appropriate representation of age, sex, ethnic, racial and socioeconomic groups in order to be representative of children with DS. Incremental measures, especially for height, are also needed so that growth velocity of children with DS can be characterized. These charts are crucial in allowing physicians to make judgments about the growth of children with DS in their care. Accordingly, the overall goal of this study is to recruit a regional cohort of infants, children and adolescents with DS through (1) a large specialty care center for children with DS, (2) an extensive regional primary pediatric care network, (3) and through community support groups, social services networks and advertising. Approximately 580 infants and children will be recruited and evaluated longitudinally (quarterly for infants, bi- annually for toddlers, and annually for children and adolescents) in order to achieve sufficient representation of age and sex groups. The evaluation will include anthropometric assessment of growth in size, body proportions and body composition in order to develop guidelines for the use of BMI for obesity screening based on measures of adiposity. Brief questionnaires to characterize sociodemographic characteristics, health history, feeding issues and physical activity will be included to characterize the sample. Growth charts will be created using the state-of-the-art approach for constructing normalized growth charts with smoothed percentile distributions for use in clinical care. Factors associated with growth failure in children with DS will be explored.